Hyperlipidemia and Lipid Assessment Flashcards
What kind of lipids are transported as lipoproteins?
blood lipids
What is in the hydrophobic core?
- cholesterol esters
- triglycerides
What is on the hydrophilic surface?
- cholesterol
- phospholipids
- apolipoproteins
5 major classes of lipoproteins
- chylomicrons
- VLDL
- IDL
- LDL
- HDL
chylomicrons - % lipid vs % protein
99:1
VLDL - % lipid vs % protein
92:8
IDL - % lipid vs % protein
85:15
LDL - % lipid vs % protein
80:20
HDL - % lipid vs % protein
50:50
Very large lipoprotein particles that carrying mainly triglycerides (much lesser amounts of cholesterol and phospholipids)
chylomicrons
proteins in chylomicrons
- major: apolipoprotein (apo) B-48
- others: apologetics’s A, C, E
Chylomicrons are formed by _______ _______ cells postprandially from dietary ____, secreted into the intestinal _____ and eventually to the blood through the ______ ______.
Chylomicrons are formed by the intestinal epithelial cells postprandially from dietary fats, secreted into intestinal lymph and eventually to the blood through the thoracic duct.
Chylomicrons: Upon delivery to ______ ________ cells, ______ are broken down by ______ _____ to release ____ _____ ____, which are taken up by tissues.
Upon delivery to vascular endothelial cells, triglycerides are rapidly broken down by lipoprotein lipase to release free fatty acids (FFA), which are taken up by tissues.
Chylomicrons: The resulting particle, a chylomicron _____, is removed from circulation by ______ receptors.
The resulting particle, a chylomicron remnant, is removed from circulation by hepatic receptors.
Contain a large amount of triglycerides and smaller amounts of cholesterol (free and ester forms) and phospholipids
VLDLs
proteins in VLDLs
- major: apo B-100
- other: app E, C
VLDLs are produced by __________ and carry _____ synthesized in the liver.
VLDLs are produced by hepatocytes and carry lipids (esp TG) synthesized in the liver.
In the blood, ______ lipase hydrolyzes ______, and the size of the particles is reduced, forming ________ density lipoprotein (__), and after further _______ of triglycerides, forming ____ density lipoprotein (__).
In the blood, lipoprotein lipase hydrolyzes triglycerides, and the size of the particles is reduced, forming intermediate density lipoprotein (IDL), and after further hydrolysis of triglycerides, forming low density lipoprotein (LDL).
derived from VLDL
LDL
Contain large amounts of cholesterol esters and smaller amounts of free cholesterol, triglycerides and phospholipids
LDLs
LDL: Each particle contains one single _________ molecule.
LDL: Each particle contains one single apo B-100 molecule.
LDL is the main carrier of ______ in blood, transports cholesterol _____ tissues
LDL is the main carrier of cholesterol in blood, transports cholesterol towards tissues
Apo B interacts with specific ____ receptors (Apo-B receptors) located on cell surfaces in many tissues, including the ___, resulting in ______ of LDL particles from the circulation.`
Apo B interacts with specific LDL receptors (Apo-B receptors) located on cell surfaces in many tissues, including the liver, resulting in removal of LDL particles from the circulation.
LDL particles with more TG characteristics
- larger, less dense
- less atherogenic
LDL particles with less TG characteristics
-“small, dense LDL”
more atherogenic
Formed as a precursor (nascent HDL) in liver and intestine
HDL
contains mainly protein and phospholipids
“nascent” HDL
HDL gains _______ and free _______ from tissues (through the action of lecithin-cholesterol acyl transferase – LCAT), also cholesterol _____ from VLDL (cholesteryl ester transfer protein – CETP), becoming “_____” HDL
Gains phospholipids and free cholesterol from tissues (through the action of lecithin-cholesterol acyl transferase – LCAT), also cholesterol esters from VLDL (cholesteryl ester transfer protein – CETP), becoming “mature” HDL
primary apolipoproteins in mature HDL
apo A-I, A-II and A-IV
HDL has an important role in _____ cholesterol transport, i.e., carrying cholesterol from ______ tissues back to the _____ for excretion as ____ acids and bile _______.
HDL has an important role in reverse cholesterol transport, i.e., carrying cholesterol from peripheral tissues back to the liver for excretion as bile acids and bile cholesterol.
lipid profile/panel
- total cholesterol (TC)
- triglycerides (TG)
- lipoproteins - HDL-C, LDL-C, VLDL-C
Measure actual amount of triglycerides in the _______
Measure actual amount of triglycerides in the specimen
necessary for differentiating between TG in chylomicron (diet) vs. VLDL (liver)
fasting specimen - 12 hours optimal
______ has minor effects on cholesterol measurement but normally results in ________ depletion (eliminates postprandial TG)
Fasting has minor effects on cholesterol measurement but normally results in chylomicron depletion (eliminates postprandial TG).
indicator of metabolic syndrom
triglycerides
Use as an independent CHD risk factor is controversial
triglycerides
Increased risk for _____ _________ at levels > 400 mg/dL (most significant > 1000 mg/dL)
Increased risk for acute pancreatitis at levels > 400 mg/dL (most significant > 1000 mg/dL)
Causes of elevated TGs
- obese/overweight
- physical inactivity
- cigarette smoking
- excessive alcohol intake
- high carb diets (esp simple)
- various diseases i.e. T2DM, renal failure
- drugs i.e. estrogens, corticosteriods
- genetic dyslipidemia
What causes of elevated TBs can lifestyle modification target?
- obese/overweight
- physical inactivity
- cigarette smoking
- excessive alcohol intake
- high carb diets (esp simple)
Assessment of cholesterol from all lipoprotein forms (chylomicron, VLDL, LDL, HDL) – measure actual amount
total cholesterol
TG > _____ mg/dL (from chylomicrons or VLDL) reduces accuracy of ___ and ____ measurement
TG > 400 mg/dL (from chylomicrons or VLDL) reduces accuracy of LDL and VLDL measurement
how is HCL assessed
like total cholesterol, HDL is measure
HDL measurement: ____ and _____ are precipitated, leaving HDL as the only ______-containing lipoprotein (i.e., the profile measures total and HDL cholesterol)
HDL measurement: LDL and VLDL are precipitated, leaving HDL as the only cholesterol-containing lipoprotein (i.e., the profile measures total and HDL cholesterol)
how are LDL and VLDL assessed
calculated values
LDL calculation
LDL-C = (TC) – (HDL-C) – (TG/5)
VLDL calculation
VLDL-C = TG/5
non-HDL goal
Non-HDL-C goal: LDL-C goal + 30 mg/dl
causes of low HDL
-Elevated triglycerides
-Overweight and obesity
-Physical inactivity
Cigarette smoking
-Very high carbohydrate intake
-Type II diabetes
-Certain medications (e.g., beta-blockers, anabolic steroids, progestational agents)
primary cause of hyperlipidemia
hereditary
secondary causes of hyperlipidemia
- Obesity
- High calorie diet
- High TG and saturated fat diets (increases cholesterol synthesis)
- ↑ VLDL production (high refined carbohydrate diet)
- Sedentary lifestyle
- Diabetes
- Other such as hypothyroidism, medications
Fredrickson Classification of Primary Hyperlipidemias: Type 1
- creamy top
- chylomicrons
- Lipoprotein lipase deficiency, Apo-C2 deficiency
- serum TC normal
- serum TG elevated ++
Fredrickson Classification of Primary Hyperlipidemias: Type 2a
- clear
- LDL
- Familial hypercholesterolemia, Polygenic hypercholesterolemia, Familial combined hyperlipidemia
- serum TC elevated ++
- serum TG normal
Fredrickson Classification of Primary Hyperlipidemias: Type 2b
- clear
- LDL, VLDL
- Familial combined hyperlipidemia
- serum TC elevated ++
- serum TG elevated +
Fredrickson Classification of Primary Hyperlipidemias: Type III
- turbid
- IDL
- Familial dysbetalipoproteinemia
- serum TC elevated +
- serum TG elevated +
Fredrickson Classification of Primary Hyperlipidemias: Type IV
- turbid
- VLDL
- Familial hypertriglyceridemia, Familial combined hyperlipidemia, Sporadic hypertriglyceridemia,
- Diabetes*
- serum TC normal/elevated +
- serum TG elevated ++
Fredrickson Classification of Primary Hyperlipidemias: Type V
- creamy top, turbid below
- chylomicrons, VLDL
- Diabetes
- serum TC elevated +
- serum TG elevated +
Mutation in LDL receptor preventing LDL uptake, resulting in elevated LDL levels at birth and throughout life
familial hypercholesterolemia (type IIa)
Co-dominant genetic disorder, both heterozygotes (1/500) and homozygotes (1/1M) are affected
familial hypercholesterolemia (type IIa)
- Increased production of VLDL and LDL
- Elevated cholesterol and triglycerides
Familial combined hyperlipidemia (type IIb)
Autosomal dominant (1/50 to 1/100), unknown etiology
Familial combined hyperlipidemia (type IIb)
- Results from impaired chylomicron and VLDL clearance
- High chylomicrons and VLDL, increased TC and TG
Familial dysbetalipoproteinemia (type III)
- Multiple defects, varying inheritance patterns
- Exacerbated by obesity, diabetes, hypothyroidism, alcohol, chronic kidney disease
Familial dysbetalipoproteinemia (type III)
- Increased VLDL
- Elevated TG
Familial hypertriglyceridemia (type IV)
- Autosomal dominant (1/100), clearance defects
- Associated with insulin resistance
Familial hypertriglyceridemia (type IV)
hyperlipidemia risks: elevated cholesterol, especially high LDL and reduced HDL
- atherosclerosis
- xanthomas and xanthelasmas
collections of foam cells (cholesterol) - larger and in skin, tendons
xanthomas
collections of foam cells (cholesterol), smaller and generally on the face esp around eyes
xanthelomas
